Circulation. 2001;103:2885-2890
Published online before print May 29, 2001, doi: 10.1161/hc2401.092816
Published online before print May 29, 2001, doi: 10.1161/hc2401.092816
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(Circulation. 2001;103:2885.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Increase in Circulating Endothelial Progenitor Cells by Statin Therapy in Patients With Stable Coronary Artery Disease
From the Division of Molecular Cardiology, Department of Internal Medicine IV (M.V., S.F., K.A., A.A., A.M.Z., S.D.) and the Department of Hematology, Internal Medicine III (H.M.), University of Frankfurt, Theodor-Stern-Kai 7, Frankfurt, Germany.
Correspondence to Andreas M. Zeiher, MD, Dept of Internal Medicine IV, University of Frankfurt, Theodor Stern-Kai 7, 60590 Frankfurt, Germany. E-mail Zeiher{at}em.uni-frankfurt.de
Background—Therapeutic neovascularization may constitute an important strategy to salvage tissue from critical ischemia. Circulating bone marrow–derived endothelial progenitor cells (EPCs) were shown to augment the neovascularization of ischemic tissue. In addition to lipid-lowering activity, hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) reportedly promote the neovascularization of ischemic tissue in normocholesterolemic animals.
Methods and
Results—Fifteen patients with angiographically
documented stable coronary artery disease (CAD) were
prospectively treated with 40 mg of atorvastatin per day for 4 weeks.
Before and weekly after the initiation of statin therapy, EPCs were
isolated from peripheral blood and counted. In addition,
the number of hematopoietic precursor cells positive for CD34, CD133,
and CD34/kinase insert domain receptor was analyzed.
Statin treatment of patients with stable CAD was associated with an
1.5-fold increase in the number of circulating EPCs by 1 week after
initiation of treatment; this was followed by sustained increased
levels to 3-fold throughout the 4-week study period. Moreover, the
number of CD34/kinase insert domain receptor–positive hematopoietic
progenitor cells was significantly augmented after 4 weeks of therapy.
Atorvastatin treatment increased the further functional activity of
EPCs, as assessed by their migratory
capacity.
Conclusion—The results of the present study define a novel mechanism of action of statin treatment in patients with stable CAD: the augmentation of circulating EPCs with enhanced functional activity. Given the well-established role of EPCs of participating in repair after ischemic injury, stimulation of EPCs by statins may contribute to the clinical benefit of statin therapy in patients with CAD.
Key Words: coronary disease • angiogenesis • endothelium
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